Description: (Applicant's Description) The Neurologic Oncology Program includes members of the University of California San Francisco Department of Neurological Surgery's Brain Tumor Research Center (BTRC) and Neuro-Oncology Service (NOS). The Program offers state-of-the-art research and therapy for children and adults with central nervous system tumors, and is supported by numerous grants including a Program Project Grant (PPG) and the North American Brain Tumor Consortium grant (NABTC). The NOS evaluates over 500 new patients each year, and many enter a clinical research protocol involving radiation therapy and chemotherapy. In this multidisciplinary Center, clinical and basic science investigators work closely together to find and test more effective therapies, seeking to improve therapy for brain tumors and the disorders accompanying them. Major scientific thrusts include work in brain tumor cellular and molecular biology, molecular genetics, drug analysis, drug resistance, radiobiology, radiation resistance, normal tissue tolerance, and brain injury. Major clinical thrusts include the design and conduct of phase I, II, and III trials of therapies for children and adults with newly diagnosed or recurrent brain tumors. Molecular epidemiology is a major effort, as well, with specific research programs evaluating potential familial components in the etiology of adult brain tumors. During the next three years, research will emphasize the local delivery of radiation and other agents directly into tumor. Protocols include phase I and III trials of low-activity, permanent iodine-125 brachytherapy and Gamma-Knife radiosurgery with metalloproteinase inhibitors; and phase II trials of systemically delivered chemotherapy and local delivery of gene therapy. Correlative clinical data support for laboratory studies by BTRC and Cancer Center researchers will come from these trials. The Neurologic Oncology Tissue Bank will support laboratory projects including evaluations of radiation sensitivity and the molecular basis for radiation response. Magnetic resonance spectroscopy (MRS) will be used to assess primary tumor volumes, treatment effects, and failure patterns. Clinical, radiographic, and laboratory correlations will form a basis for individualized specific treatment recommendations, which we hope will control malignancy with minimal or no toxicity.